Tuesday, 15 November 2016

Preventing Auto-Immune Disease and some Autism

I think it is common sense to say that preventing a problem from developing is much wiser than trying to solve it later on. This is a recurring issue in both life and medicine.

In the research we now see preventative measures developed to reduce the risk of cancer, we also see how some interventions are only effective when started very early.

In the case of autism we have seen than often it is caused by a myriad of factors that by themselves might have been harmless but when taken together are the multiples hits that caused the brain to develop differently.

Much research looks individually at these factors that increase the risk of autism. In the wider media much disdain is directed to these findings as if each factor is THE cause of autism and how can so many things cause autism. But by understanding these factors you can then set about countering them.

I did create my simplified schematic to explain classic autism a while back. It is not perfect but it does illustrate much of what is going on.

I do get occasional questions about reducing the risk of autism. For example, Monty now aged 13 with ASD, has a big brother and he wants to know. Our reader, Kritika from India, has also raised this issue. If you have autism in your family you may well decide you would like to minimize the risk of more cases.

In practical terms, you cannot change your genes or those inherited epigenetic markers. Maybe this will change in future. But there are things you can do.

We know that oxidative stress is a driver of much disease including autism. This can be minimized by lifestyle changes and indeed with a little pharmacological help.

I was interested to see a study that used NAC to treat mothers who suffer unexplained pregnancy loss, the antioxidant showed a “significant increase in the take-home baby rate”. I was really just looking for safety information.

Pregnancy could be associated with a state of oxidative stress that could initiate and propagate a cascade of changes that may lead to pregnancy wastage. This process of oxidative stress may be suppressed by the antioxidant effect of N-acetyl cysteine (NAC). The current study aimed to evaluate the effect of NAC therapy in patients diagnosed with unexplained recurrent pregnancy loss (RPL). The study was a prospective controlled study performed in the Women's Health Centre, Assiut University, Egypt. A group of 80 patients with history of recurrent unexplained pregnancy loss were treated with NAC 0.6 g + folic acid 500 microg/day and compared with an aged-matched group of 86 patients treated with folic acid 500 microg/day alone. NAC + folic acid compared with folic acid alone caused a significantly increased rate of continuation of a living pregnancy up to and beyond 20 weeks [P < 0.002, relative risk (RR) 2.9, 95% confidence interval (CI) 1.5-5.6]. NAC + folic acid was associated with a significant increase in the take-home baby rate as compared with folic acid alone (P < 0.047, RR 1.98, 95% CI 1.3-4.0). In conclusion, NAC is a well-tolerated drug that could be a potentially effective treatment in patients with unexplained RPL.

This then made be recall a US fertility clinic, that our reader Roger once mentioned in a comment.

“At Braverman Reproductive Immunology, we believe Autism Spectrum Disorder (ASD) and various pregnancy and infertility complications (listed below) appear to have the same cause. In fact, we have found that a large number of patients who present to our center with the below complications already have a child with ASD.

This discovery started us on the journey to see if ASD itself could be prevented while treating other associated conditions. We believe treatment for these common issues will not only prevent the pregnancy complications listed below, but may alsoprevent ASDin the group of patients that have already had a child with ASD.”

Dr Braverman does not mention oxidative stress, but perhaps he should.

So step one would be to reduce oxidative stress during pregnancy, via lifestyle changes and taking antioxidants.

Step two would be to avoid inflammation, Dr Braverman refers to the link to auto-immune disease and miscarriage/autism.

We know that maternal inflammation is one of the easiest ways to cause autism in mouse models (the MIA model - Maternal Immune Activation).

We have some research to show that the risk of auto-immune disease can indeed be reduced and indeed that the risk of progression from minor to more major auto-immune disease can also be minimized.

We even have a tiny study showing that immuno-modulatory therapy using a probiotic during pregnancy can reduce incidence of ADHD and autism. For me ADHD is just a case of autism-lite.

Background:

Recent experimental evidence suggests that gut microbiota may alter function within the nervous system providing new insight on the mechanism of neuropsychiatric disorders.

Methods:

Seventy-five infants who were randomized to receiveLactobacillus rhamnosusGG (ATCC 53103) or placebo during the first 6 mo of life were followed-up for 13 y. Gut microbiota was assessed at the age of 3wk, 3, 6, 12, 18, 24 mo, and 13 y using fluorescein in situ hybridization (FISH) and qPCR, and indirectly by determining the blood group secretor type at the age of 13 y. The diagnoses of attention deficit hyperactivity disorder (ADHD) and Asperger syndrome (AS) by a child neurologist or psychiatrist were based on ICD-10 diagnostic criteria.

Results:

At the age of 13 y, ADHD or AS was diagnosed in 6/35 (17.1%) children in the placebo and none in the probiotic group (P= 0.008). The mean (SD) numbers ofBifidobacteriumspecies bacteria in feces during the first 6 mo of life was lower in affected children 8.26 (1.24) log cells/g than in healthy children 9.12 (0.64) log cells/g;P= 0.03.

Conclusion:

Probiotic supplementation early in life may reduce the risk of neuropsychiatric disorder development later in childhood possible by mechanisms not limited to gut microbiota composition.

The issue, as with NAC during pregnancy, is whether immuno-modulatory therapy is safe.

The study on ADHD and autism was actually a study looking at whether a certain probiotic if given during pregnancy could reduce eczema later on in the child.

Early-life exposure to dogs is protective against allergic disease development, and dog ownership is associated with a distinct milieu of house dust microbial exposures. Here, we show that mice exposed to dog-associated house dust are protected against airway allergen challenge. These animals exhibit reduced Th2 cytokine production, fewer activated T cells, and a distinct gut microbiome composition, highly enriched forLactobacillus johnsonii, which itself can confer airway protection when orally supplemented as a single species. This study supports the possibility that host–environment interactions that govern allergic or infectious airway disease may be mediated, at least in part, by the impact of environmental exposures on the gastrointestinal microbiome composition and, by extension, its impact on the host immune response.

One of my views is that by early treatment of autism you may indeed reduce the risk of epilepsy. The key here is “reduce the risk”, it does not mean there is no risk. There are likely hundreds of causes of epilepsy, but if you can reduce the incidence by 30+% that would look like a big success to me.

I recall another study that looked at treating people with eczema to see if you could reduce the chance of progression to asthma. Using Ketotifen the trial showed that it was indeed possible.

To evaluate the prophylactic effect of ketotifen against the onset of asthma we selected 121 infants with atopic dermatitis, without any history suggestive of asthma (cough and/or wheezing). Sixty-one children received ketotifen twice daily. Those who weighed less than 14 kg received 0.8 mg; 14 kg or more, 1.2 mg. Sixty children, a placebo syrup indistinguishable from the active syrup. Both groups were followed for 1 year, with bimonthly evaluations. The criteria for onset of asthma were two different episodes of wheezing treated with bronchodilator drugs. Both groups were comparable regarding age, sex, weight, onset, and duration of atopic dermatitis and age at the onset of asthma. During the 1 year study, asthma was observed in eight children of the ketotifen group (13.1%) and in 25 children of the placebo group (41.6%) (P less than .001). Side effects were negligible and routine laboratory tests disclosed no significant alterations. Ketotifen is a very useful drug for prevention of asthma in children with atopic dermatitis and total IgE more than 50 IU/mL.

Somali Autism Clusters

This then takes me back to that issue I looked at long ago, which was the reason for the Somali immigrants to Sweden and US having so many children with autism. This even got termed the Swedish Disease by the migrants, they claimed to have never seen autism back home in Somalia.

Then we have the hygiene hypothesis which in effect says that, within limits, a little dirt is good for you.

Hormonal Dysfunction

We know that gestational diabetes increases the risk of autism and we also known that the mother being hypothyroid increases the risk. In some cases the hormone dysfunction is a consequence of the auto-immune dysfunction.

We also know the female hormone progesterone is extremely neuro-protective. The level of this hormone is supposed to rise during pregnancy.

In past times hormones were given to some pregnant mothers, but this went out of fashion. Perhaps this should be revisited?

Then we have the surge of the hormone oxytocin that the baby is supposed to receive at birth. This surge may be relevant to the GABA switch when shortly after birth this neurotransmitter is supposed to switch from excitatory to inhibitory as the neurons mature. If the baby is born by Caesarian there will be no oxytocin surge for the baby.

Preventing Regressive Autism Secondary to Mitochondrial Disease (AMD)

It is on open secret that doctors at Johns Hopkins have identified a variant of regressive autism called Autism secondary to Mitochondrial Disease (AMD).

It remains unclear how rare this is and absolutely nobody serious is going to research this, if they ever want to receive a research grant in the future.

We saw that in people with a genetic predisposition to mitochondrial dysfunction, an immune over-reaction to an insult like multiple vaccinations can trigger mitochondrial disease. This will present itself as autism and quite possibly severe autism in a previously unaffected child.

Those doctors treating AMD use mild immuno-suppressing drugs before any future vaccinations.

How do you minimize the chance of AMD?

The first thing is to never use paracetamol/acetaminophen in a baby or child, particularly just after vaccination. This drug may kill the pain but it depletes GSH the body’s main antioxidant, just when it needs it most. Use something like Ibuprofen.

Vaccines are given in multiples so as to save time and money and I suppose improve compliance. You might expect giving them one-by-one would actually make them more effective as well minimizing any collateral damage to a small percentage of kids.

Conclusion

As I keep reminding readers, I am not a doctor, but it would be nice if a few more doctors other than Braverman took preventing autism seriously.

I would like to know if progesterone is an effective therapy in the MIA model of autism. In this model they trigger the mother’s immune system during pregnancy which leads to offspring with autism. What would be the effect of giving progesterone? Would it protect the pups?

Are progesterone levels reduced in mice that will become autistic?

So I suppose I would trial NAC and progesterone in the mother mouse.

For everyone else it is case of choosing whether or not to make lifestyle changes to reduce oxidative stress. Improving gut bacteria can be done via probiotics, eating more (slightly dirty) fruit and vegetables, having a pet dog, spending some time in the nature.

As for vaccine risk, however small it might indeed be, there will never be a serious investigation of this, for understandable reasons.

41 comments:

Peter, it's been many years and I can't remember details but I think on my sixth week of pregnancy bleeding occured and was treated with progesterone to keep the baby.There are many times that I feel guilty having used hormone therapy and blame it for my son's disorder. On the other hand Asperger's runs in my family and I am quite sure that lot's of other factors contributed to it.

Autoimmunity is only one factor leading to miscarriage.The big one is folate metabolism.As Dr. Frye's research,and case histories of families show,there is often a triad of MTHFR mutations,folate receptor autoantibodies,and deficiencies in N-acetyl cysteine.So this study out of Egypt does not surprise me.They may only be looking at a small portion of the picture Jill James and Richard Frye has mapped out.Jill James has researched the families,mothers grandmothers,etc in great detail.

There is a long history of miscarriage,mental illness,and medical problems I now realize are folate related in my family.I know of at least one relative,born in 1930,who also had Asperger's in addition to all this.

I have all this plus many medical problems,mostly autoimmune.Another common comorbidity with those who have both MTHFR mutations,and FRAs,seems to be PANDAS or PANS,something I have often wondered if I have.Susan Swedo's research has shown PANDAS and PANS often shows up in families where there is a long history of autoimmune disease,and mental illness.I also have a rare set of mutations at 11q22.1,that are associated with cancer,ADHD,and intellectual disability.These mutations have yet to be documented with autism.So I have two distinct sets of mutations.Before my treatment with folinic acid and B12,I was verbal,but otherwise low functioning.Before this,I had multiple autistic regressions,triggered by acute infection.Starting as an infant well into adulthood.I know from talking with parents online,this is not unusual.I suspect for some,inherited autoimmunity may play a greater role in regression,triggered by fever or infection,than mitochondrial dysfunction,and there is some evidence that proves this.Since I began treatment with the folinic acid and B12 (I also have pernicious/megaloblasttic anemia.),I no longer get the acute infections,that lead to equally severe regression.

I don't doubt that women who have been shown to have all of these defects in metabolism/methylation,and autoimmunity,could prevent autism,ADHD,mental illness,or intellectual disability in future children.This is where intensive screening of women who wish to become pregnant would come in.

This is a very tough discussion for democratic nations to have as it is very hard to get the political will to ban certain lifestyle behaviors that do not literally have a 100% causal influence and 100% proven rate of harm to babies and children. Everyone knows now that lead is something to fear in your water supply because of the reduced IQ and generally reduced health to those exposed, but many people don't know that as many as 7% of USA births are estimated to have some level of FAS (Fetal Alcohol Syndrome) involved. In fact, in terms of risk factors for autism, the stress of alcohol on the fetus could in some cases by the straw that breaks the camel's back. Many women turn to drinking when they have problems conceiving (worry about their husband leaving them, worry in general about being infertile) and then when they do conceive and finally realize they are pregnant, they gloss over the fact they may have irreparably damaged their child with alcohol and other harmful substances and lifestyle choices during that time. As long as alcohol is legal and popular as a medication for stress, women are going to abuse it. In a study I linked in the topic below, it shows how alcohol abuse during adolescence has an epigenetic impact on future offspring. Whether these epigenetic markers can be reversed over time via abstinence from alcohol or through some future medication remains to be determined. On top of that, here is the USA there is a trend to legalizing marijuana at a time when a wealth of scientific evidence is now coming in rather late to the party that describes the mechanisms of how cannabis seriously harms people, but especially adolescents and perhaps even worse with unborn children. There are probably 100s of thousands of women who smoke marijuana here in the United States who actually believe that alcohol is bad for the baby but marijuana is OK. Then even on top of that are all of the "legal" psychoactive drugs many men and women take thanks to their "psychiatrist" to treat conditions such as depression that neuroscience really only superficially understands at the moment. It is not that drugs are bad, but how liberally they are prescribed and how abundant they are in the blood of millions of mothers to be here in the USA is just staggering, not to mention that much of the research on these drugs is bought and paid for by the pharmaceutical industry, rather than an independent funding source that is looking out for the common man.

Then there is the issue of promoting prophylactic measures with mass numbers of people when the misinformation spread through the press that multivitamins are harmful or useless leaves people to believe that simply eating the fruits, leaves, and stems of random plants is the only thing you need to do to be healthy when there is a lot of evidence that taking aspirin daily can reduce your risk of various cancers and cardiovascular disease, ESPECIALLY AMONG THE OBESE!

On the other hand, plenty of people have seen what I and my wife have to deal with in regards to autism, and maybe that fear in some parents-to-be could motivate people to take preventive measures. Maybe now that the cost of a full DNA sequencing of a human genome is only $1000 and rapidly plummeting in price every year will eventually give some people the tools to know some good preventative measures that should be taken to reduce the risk of autism, ADHD, schizophrenia, etc. Until then, we will probably have to wait a while before the conversation of epigenetics and how your lifestyle choices today impact your future progeny directly takes place on an informed scale in the same manner is smoking which literally took half a century to be taken seriously by the public at large after plenty of scientific evidence had been released showing how bad it is for your health.

Obesity seems to be associated with a host of health issues and in a mother to be, increased risk of gestational diabetes, high blood pressure, miscarriage and pre term delivery to name a few.

A recent study, based on observational data, published in October in the Lancet, did link not only physical health issues but cognitive performance, neurodevelopmental disorders including cerebral palsy, in children born to obese mothers.

However, a recent study also inficated that obesity could not simply be about consuming more calories. In other words, obesity might not only be a cause of lot of trouble but also an effect of a troubled physiological system. If you happen to be really obese, not just plump with a little baby fat and there, you are likely to have a pathological state which will have obvious consequences for your offsprings if you do not take help.

Kritika, a while back I wrote a post about cardiazol, a very old drug long abandoned in the west. At Stanford it is being trialed at low doses to improve cognition in Down Syndrome, via its effect on a sub-unit of GABAa receptors. I suspect this dysfunction will also be found in some autism, affecting cognition.

Cardiazol dicodid is available in India but not easy to procure it seems. I called up local pharmacies as well as ones around All India Institute of Medical Sciences, where one has the highest chances of getting medicines. I would start with cardiazol and the moment I as much as spelled out dicodid, person on the other side would turn curt and in a hurry to hang up, leaving me feeling like a desperate junkie. There has been so much hue and cry, rightly so, about codeine abuse, even amongst young school going population, that it seems the drug is not up for easy otc sale.

The description, however, in your post, about the role of fear and seizure induction and electroconvulsive therapy evoked a mild discomfort..one flew over the cuckoos nest types?

It seems in India and probably elsewhere, electroconvulsive therapy is being revived minus the fear factor. The patient is not conscious while he undergoes the treatment which makes it not too uncomfortable and has shown promising results in certain individuals.

Sure obesity requires treatment, but not getting it treated has strong causal evidence in harming the children born to obese women. It is no longer a simple issue of society being tolerant of unhealthy body types, this is an issue that can have a strong effect on multiple generations into the future for those obese women who choose to have children.

If you saw a pregnant woman chugging a beer, would you find that disdainful? Well obesity might be just as bad on the baby (how much alcohol a woman drinks and how obese the woman is obviously matter).

Nevertheless, there is some hope with some new research (no paper) from the society of neuroscience convention that everything we have all been talking about on this blog with BioGaia, L Reuteri, and complications from obesity intersecting in a very interesting way:

This of course is in mice, but what they found is that obese mice generally produced pups that displayed some autism symptoms, in particular a lack of interest in being socialable. They also found in these mice that the neurons in a reward pathway of the brain (I am guessing the Nucleus Accumbens) have little to no oxytocin being produced, and that the neurons in this reward circuit fire less when obese mice offspring meet up with other mice (i.e. less interest in socializing). On top of that, the gut bacteria strain L Reuteri was almost totally absent in these mice. Of course L Reuteri species in humans and mice are different, but pretty much all types of L Reuteri in these obese mother offspring mice were devoid of type of bacteria.

But the exciting thing is when they added L. Reuteri to the drinking water of these mice, their oxytocin levels increased as well as their sociability. Repetitive behaviors unfortunately persisted.

The so-called ventral striatum (Nucleus Accumbens) is the core cortical brain area for reward and it pretty much gets hijacked in drug addiction. This is the area L. Reuteri helped normalize oxytocin levels in obese offspring mice. The dorsal striatum (sometimes referred to as the caudate nucleus and putamen) is the area of the brain that is most dysfunctional in OCD and has been linked in various disorders to repetitive behaviors. The most compelling research I have seen suggests mglur5 receptor dysfunction in this area of the brain is what goes wrong in autism, thereby leading to repetitive behaviors.

In Greece there is a painkiller called Lonarid, which is acetaminophen with codeine and caffeine. It is an OTC drug but you can only have one packet per month. When I used it for severe pain, my son didn't respond well and I think this was due to codeine. He felt even worse with it.

I have read that piece about fat mother mice, rather mother mice fed on a diet to induce obesity giving birth to pups with a different gut flora and less sociability versus mother mice fed on a regular diet with pups who were social and had l.reureri in their gi tracts.

I am not countering that obesity or smoking or alcohol are dissociated with any risk to the progeny.

But I have strong objection to obesity being treated as a lifestyle choice..as much as I object to your portrayal of women consuming alcohol when unable to conceive in the fear of being deserted by their husbands. Or did you write that in a lighter vein.

I have to say in autism research there is a skew towards blaming Mom. In fact, it is EVERYWHERE!! Intelligence, they say, is more based on Mom, than Dad. Autism, it's more Mom than Dad. In fact, I think, based on researchers' analyses, my boys should act like me, talk like me, and basically be mini me's. But, they don't. In fact, if my mother's intelligence was the sole basis for my intelligence, I sure as hell wouldn't have been able to do multivariable calculus. That's pure Dad. In fact, even the immune activation mouse always makes me feel like I need to tilt my head and squint, like I'm looking at a skewed canvas. Women used to get sick when they were pregnant...and it didn't make anyone blink twice. Now, if only Dr. Naviaux would get his research results published. By the way, Peter, Dr. Richard Frye just published some interesting stuff about Leucovorin. Not sure if you had seen it.

Well I am not sure which country you said you were from, the here in the United States we have a lot of problems of our own making and obesity, drugs, and alcohol abuse are just some of them.

About 20 years ago, there was a push among some in popular culture for women to "love their bodies" no matter what their body looked like. Anorexia was the big problem in the news at the time while these days you almost never hear about it anymore as the pendulum has swung to the opposite direction and some 300 pound women literally think that if anyone finds them unattractive, then there is something wrong with the people judging them. Fat shaming may have induced some people to have eating disorders such as anorexia, but it is hard to argue that it didn't also help keep obesity rates down to a level that literally does not threaten the very survival of future generations. As an example, our military is having extreme recruiting challenges because the younger generation is simply too unfit to serve even if they want to.

Simply put, becoming obese is still not taken seriously in American culture because literally 40% of women now are obese (35% men) and 70% of women are overweight. Other than maybe Great Britain, you can't find these levels of obesity anywhere else in the world and if you track autism rates as well as the rates of ADHD, and correlate them with the increase in the rates of obesity, you see something shocking there. Of course, correlation does not mean causation, but the causative research in animal models (such as the one I just cited) is really making this a topic society cannot just ignore anymore.

Even though obesity can be strongly inherited via genetic and epigenetic factors, treating it comes down to dealing with treating food as an addiction as plenty of studies have shown that a reduced intake of calories and moderate exercise will cause just about anyone to lose weight over time. As you lose weight you will need to decrease your calories. Also, during that time many people are miserable because dieting is not something people would typically do until the very modern age as people other than elite nobles or members of an upper caste rarely had enough food to keep them satiated all the time. The problem now is that people are not motivated to put themselves through the pain and suffering you have to go through to eat less food than your brain is telling you that you need. This is a problem of addiction and willpower and choice. Cancer patients often have the stark choice of going through the pain and suffering of chemotherapy or dying, but most choose chemotherapy unless they sincerely believe nothing else can be done. Obesity needs to be taken as seriously as cancer itself, especially since one of the greatest risk factors for all cancers is obesity itself.

The Okinawans (an island of Japan) famously have a saying that you should always stop eating before you feel full (obviously the saying is in Japanese), and the Okinawans are some of the healthiest and long-lived people on the planet.

Here in the United States the average expected lifetime of a person here actually decreased last year. Among white middle aged caucasian women in particular, there has been a huge decrease in life expectancy in the last decade and most attribute this to obesity, drug, and alcohol abuse among this ethnic group. Unhealthy women will produce unhealthy children and until society understands it that your health (both men and women as plenty of recent research suggests male lifestyle factors have a big impact on future progeny) is not just a matter of your own liberty, but also of responsibility to the next generation, people are not going to make the positive effort to make losing weight (and keeping it off) a priority in their lives.

I'm from America. Not fat. China and Japan do not have the "obesity epidemic" we have here in the good ole US of A, and they are still having an "autism epidemic". Especially Japan. The autism rate there was 161 out of every 10,000. That blows the rate in the US out of the water. I don't think Japan is a nation of fat people. Those numbers were from July 1, 2015 from a source called world atlas. Next, is the UK, then Sweden, then Denmark, with the US coming in 5th. There was also an article in the WSJ about China's uncounted autistic children. My husband had ADD as a child, and his Mom would have barely hit 100 pounds, soaking wet. My husband is also thin. I see lots of horribly obese women with social, "normal" children. I think we're barking up the wrong tree here. Now, I think being obese can lead to low birth weight/preemie babies. But, given that my baby that is autistic was nearly 9 pounds and 20 inches tall at birth, and full term, there has to be something else. I actually gained less weight with him than with my first "normal" child. I also breastfed. Oh, and I never drank, never used drugs. That being said, I don't think it would hurt anyone to watch what they eat a little more closely. But, I don't think obesity is the answer to the autism epidemic. Both of my children did have to be delivered via c-section.

You will have to find the different "biotypes" before you can "blame" anything for autism. And, even then... But, let's go easy on Mom. We've already had the refrigerator Mom theory. Unless you've experienced being pregnant, and thinking oh, dirt sounds really yummy right now, you really don't know what it's like to want to rip the entire world's head off in one collective blow (otherwise known as PMS). Estrogen is a beast that only the most skillful can ride, and I've yet to meet a man who was up to it, though some do try. :)

Megan, Do not even mention the raging hormones here or some of the male readers will conclude that your comments with that confrontationist tone must have been written under the influence of PMS. Next thing you know somebody will come out with a study where they will link incidence of PMS, hence temporary insanity or better still, hysteria, with autistic progeny.

Somewhere I suspect that too much 'barking up the wrong tree' is a response to the discomfort most males feel in finding great affinity with autistic traits.

Hate to see my comment degenerating into a male versus female issue as I do feel that we can't deny biology owing to which females might be having greater influence on and hence responsibility towards the children they bear.

I am not trying to hurt anyone's feelings here but diabetes/gestational diabetes and caesarean delivery (the evidenced is mixed here) are proven in multiple studies (multiple as in dozens) as providing negative neurodevelopmental outcomes (including autism) for those born under those conditions, while obesity itself is a major risk factor as well. Not to mention, obese people have worse immunity and infection during pregnancy due to a poorly functioning immune system is also strongly associated with a big increase in risk for autism.

On top of that, there are many animal model studies now that show the multiple mechanisms about how an obese mother's poor health choices may cause harm to her children.

This is not a male versus female issue as negative health outcomes via obesity in males has been shown to be inherited now through germline manipulation of microRNA's that get passed on to their progeny via the sperm. Of course, obesity in males has yet to be shown as damaging to the baby as obesity in females, but considering an enormous percentage of obese men (I forget the numbers) are infertile due to low sperm count and poor quality sperm, this shows the need for men and women in the west to get their butt off the couch if not for themselves, than for the fact they are harming future generations by not taking their health seriously until it is too late.

Also, there is a big difference (no pun intended) between women having a shapely healthy figure or maybe even being a tiny bit overweight, and morbid obesity. And the logic that "well I have seen obese women without autistic children" does not fly in the face of the evidence because there are plenty of children who are born without strong symptoms of asthma or fetal alcohol syndrome as a result of their mothers smoking and drinking during pregnancy, or else being exposed to a poor environment if they end up being pregnant in a city with toxic air like Beijing.

Really, this is just supposed to be an intellectual discussion about what is one of the biggest overlooked risk factors or perhaps even the biggest risk factor for autism in the anglo countries at the moment besides perhaps overdiagnosis relative to other nations with less sophisticated and accessible health care systems.

Here is some food for thought with respect to this intergenerational discussion of preventing autism:

https://www.sciencedaily.com/releases/2016/11/161114142808.htm

This study discusses transposons, AKA "jumping genes" which in addition to the oxidative stress theory of DNA mutation and aging are a strong competing theory in aging called the "transposon" theory of aging. As people age, the protein complex that wraps their DNA together (collectively called chromatin) unwinds more and more for reasons not really understood at this time. High levels of polyamines like spermidine (which decrease with aging as well) are thought to help keep chromatin packed tightly which seems to be important in the general health of a cell, or at least with regards to the cell not entering a state of senescence. The transposon theory of aging posits that because chromatin becomes looser and DNA unwinds more and more from a tightly packed state, more and more of these transposons, which are normally inaccessible for being expressed, are increasingly exposed and expressed leading to further and further rates of mutation of the DNA within the cell.

What this study models are two types of transposons that seem to compete with each other in a predator/prey relationship cycle which the authors of the paper relate to how the populations of rabbits and wolves oscillate over time.

What is interesting here is the old adage of some undesirable traits in people "skipping a generation" when viewed from the finding in this study that these transposon cycles extend beyond a single human lifetime (and no doubt are involved in germline cells), which means from a complexity standpoint, looking back more than one generation for symptoms of autism in a family tree may (this is pure speculation on my part) may be necessary, rather than simply looking at the parents and how their genes are expressed. Transposons, unlike epigenetic mechanisms, directly mutate DNA by jumping around and copying themselves which affects the expression of other protein coding genes that they insert themselves next to or else remove themselves from.

So you could (my hypothesis only) have a situation where a grandfather has Asperger's or high functioning autism because certain genes are expressed more than others, then due to these transposon cycles you end up having typical children, and then those typical children end up having children, but their germline cells are mixed up a bit more from these transposon cycles, leading them to potentially have the right brew of gene expression to help facilitate autism in addition to all of the other genetic, epigenetic, and environmental risk factors.

Here is some research on Alzheimer's (the type I wish was repurposed towards autism research) that shows how an FDA approved antibiotic successfully enhanced glutamate transport (hello autism).

https://www.sciencedaily.com/releases/2016/11/161115150237.htm

I have no idea if this drug would specifically help with intellectual functioning in cases of autism where there seems to be too much glutamate accumulating at the synapses even if the levels of glutamate may not be systemically high in the body, but there is only one way to find out for sure.

With respect to the topic at hand, the largest neuroscience conference in the world wrapped up today and where a lot of new autism research was presented. https://www.spectrumnews.org has an excellent synopsis of all the autism related stuff.

Here is one presentation at the conference that was discussed (no paper):

which discusses a deficit of cyclic AMP (cAMP) shared among a wide variety of people with severe idiopathic autism as a potential common pathway for inducing severe autism symptoms. I know Peter has discussed quite a bit about cAMP here, but there were some other findings they had which go against some of the research I have read about proteins like mTOR and how they relate to autism. Again there is no paper as this was just a presentation, but you can all read the article yourselves as I found it very interesting because finding a universal dysfunctional pathway in severe autism has been daunting to date.

Probably no huge surprises that their findings most strongly linked autism to schizophrenia in one of the subtypes, but the other subtype was most strongly linked to schizophrenia or major depressive disorder (not sure what the ambiguity means or if it was a typo).

According to "Autism: Current theories and evidence"https://books.google.gr/books?isbn=1603274898Maternal Immune activation could also be linked to periodontal disease which I think has something to do with us.I try to treat periodontal attacks I experience with L reuteri ATCC PTA 5289 plus 17938.In the book there is a conclusion that testing a possible association with autism could also be worthwhile.

Maternal and paternal and lots of other relatives eating disorders profile might also give some clues. One of some autism core symptom is in fact an eating disorder which is described as picky eating, starvation, and generally fear/anxiety of food, accompanied with periods of obesity and metabolic syndrome.

Yes, this is so true. Both of my most afflicted kids (I have 3 with an autism diagnosis out of 4 children) have weight problems that blew up about age 3-4 during the winter months when I could not take them for long walks. Once I started adding supplemental fiber into their diet, this helped deal with their appetites and their last pediatric checkups have shown their growth curves with weight to be stabilized/reducing relative to where they should be for their age.

Incidentally, here is a great study I just read today (it is long but well worth the read) that showed a new mechanism of how a fiber free diet or even one without any whole plant fiber (they called it a prebiotic diet) leads to the erosion of the mucus lining the epithelium of the digestive tract due to the gut microbiota literally eating the mucus for food since there are no polysaccharides for them to munch on, due to a low fiber diet:

http://www.cell.com/cell/abstract/S0092-8674(16)31464-7

One of the most interesting takeaways is that they suggested that even though some prebiotics may be great for SCFA production, but they won't do much for preventing this mucus degrading effect which seems to be critical in helping to prevent disease and inflammation in the gut. The fiber supplementation I personally use is a home brew combination of potato starch, barley flour, and inulin, but in light of this research I might have to consider ways of getting my children more fiber from sources with intact plant cell walls. I will say that perhaps I am doing something right because there have been some nasty flu and colds going around in the last couple years, and my kids have almost never been sick (and neither have I). This was not the case before they got daily supplemental soluble fiber in their diet. Of course this is all anecdotal and flu season is about to hit my areas of the United States, so I could be suffering miserably from some flu or cold in the coming weeks, but I have found it strange that my family seems to have been spared a lot of misery for whatever reason. Oh yah and the only member of my family who has gotten sick off and on the most has been my wife who does not take regular supplemental fiber and does not exactly eat what I would call a healthy diet that has a lot of natural fiber in it. Again this is all anecdotal so maybe it is time to cross my fingers when the holidays roll around (-:

Peter, my son is challenged with a kind of attack with trembling coming from the thorax area, together with excessive sweat especially in hands?I know it can be a fear response but I was wondering if there may be other implications.

At a regular check up sugar levels seem fine. I do suspect prediabets and need to work on this.My son is supposed to not have seizures but I doubt it. There are 180 identified kinds of seizures and probably some not identified yet.I do indeed perceive all these weird things happening as seizures.

Oxidative stress, I agree. So few people see it as fundamental to disease. In the case of ASD, I see a lot of it coming from slow SUOX, XDH, and AOX1 genetics and lack of molybdenum, either the mineral itself or molybdopterin.

When these genes are slow there will be a build up in O2 in the mitochondria. Any electron that hist the O2 will turn them into superoxides. Note that all those genes have to do with environmental detoxification.

I have aspergers and Molybdemun changed my life. And in all the genes I have for autistic children I see rare gene SNPs in those genes.

Slowing SUOX will also result in a rise in glutamate since sulfites inhibit glutamate dehydrogenase.

Sometimes hypoglycemia induces a seizure like condition.. I remember your son had not eaten for twenty four hours. Could that have complicated things.

My father who was on insulin to manage steroid induced diabetes used to have these sudden spikes as the body would produce insulin in a spurt and that along with the injected insulin resulted in hypoglycemia. The condition it triggered was quite similar to what you observed in your son.

Me and my husband don't show signs of diabets, only my mum, in an older age has had high blood sugar, not established as diabets and controls it with a pill (sitagliptin).As I read now it's for diabets type 2 and usually prescribed with metformin (you can read Peter's relevant post).

My gastrenterologist directed me for abdomen blood-urine-magnetic check up and told me to visit an endocrinologist for further investigation.

My son was born almost 4 kilos and two weeks earlier. My niece (16y with neurological problems), from my husband's sister was also born overweight. I remember her doctor, specializing on metabolic syndroms, during neonatal examination, explaining that such babies have greater possibility to develop diabets later in life and we should keep that in mind.

This time my gastrenterologist paid more attention to my claim that there must be a metabolic syndrom because, although he was not the one in charge to treat my son's last infection, he followed the course and got confused with my son's immune response.Morover, and this may sound "chatty", still don't mention it for the chat itself but to give an example of how autism strikes in an indistinguish and indiscriminate way, Doctor told me that he suspects his almost 3 year old nephew from his twin brother to have autism but his parents don't accept it. Doctor has just had a baby and told me that he had a personal interest for my son's case report.

Hi Petra,Was curious about your doctor's brother being an identical twin or otherwise.

To further add to the chat, a doctor couple I know with a severely afflicted child with autism was recently visited by their old friends, another doctor couple who are suspecting their three year old to be autistic.

Petra, sometimes I do wonder if females who pursue education, the real nerve wracking, rigorous, brain burning one, are more susceptible to bearing children with autism. Maternal education and maternal inflammation? It would be interesting to generate data that might link female education alone, not maternal age which might covary with it, to incidence of neurodevelopmental disorders in kids born to them.

Did God really intend women to limit their imagination to home and hearth. I do not mean this in a negative way at all as I am quite happy to be 'just a housewife' after having gone through the rigors of higher education. What if we do find a relation between stressful education and career choices and problems with children birthed by such mothers. After years of bearing humiliation and condemned for being that unstimulating, dumb housewife who cannot think beyond the pot and the pan and bears children which is something that even animals can do and probably better, now women are facing predicament of a totally different kind.

I also suspect maternal "brain burning" profile, as you very well put it, has something to do with autism and neurological diseases.Having the tendency to (ab)use your brain sometimes lead women to a higher education pursue and maybe this is part of the "inflammation". Ruminating, problem solving, putting things in order, while recognizing the chaos and observe yourself and others playing different roles in an attempt to represent life...constantly moving brain.I believe MIA model could be a usuful scientific tool as long as you can identify your phenotype there. I don't get offended, it's not a "witch hunting" issue.Whenever I am put into the MIA model it's not me as a subject with hundreds of expressions,it's me as an object charged with particular non qualities. They can make me obese, anorectic, smoker, alcohol/drug abuser, refrigerated, disordered, whatever.. MIA model is a lab condition, and as Peter I think says, it's strange in how many ways they can make mice autistic. Practically nothing is as stable as that and mum is changing all the time, before, during, after pregnancy, but I can accept that the emotional and physical stress remains.Metaphysical and deterministical explanations usually don't lead me anywhere.

Kritika, I am glad it was you that noted the link between education and risk of autism. Nobody is going to research this, but look at how many very clever people (professors etc) have relatives with autism. If you looked at what happens when educated alpha male marries educated alpha female I think you would see the same. You might then conclude that going to work in a stressful job while pregnant is unwise for those with other risk factors. I think this will only apply to some sub-types of autism. There will be many kids with autism whose parents are not rocket scientists.

Clearly stress is not good for you and the unborn child is not as robust as we might have thought, and needs protection.

Had gone for a week's stay to my parents place without the bioamicus reuteri and my son's social behaviour seemed to deteriorate a little. Now we are a strongly opinionated, a little loud family, where every one thinks that everybody else is a fool and the only circumstance under which you will find any two members having an amicable discussion is when they are criticizing a third one. So there is lot of energy flying and flowing around and probably that adds to my son's lousy behaviour and tantrums or it could have been a combination of things. He was just acting like a spoilt brat and I was thinking of what lies ahead.

Back home, and after day and a half of the probiotic, he seems back to normal. The probiotic took effect only after some digestive issues which led to gas were resolved. So you see, it is such a delicate balance and any intervention will give it's greatest benefit only when my son has an absolutely clean intestine. My husband watching my son struggling and tantrumming with his studies two days back felt that we should add back bumetsnide. But you see, with indigestion relieved, yesterday he did quite well.

Coming to after effects of bumetanide withdrawal, things seem to have just stuck..all kinds of things.

Cognitive gains seem to have stuck. Better handwriting and good pencil grip. Some kind of enhancement in gross motor skills..his movements. He never had issues with those but a little more body awareness. Developing ability to catch and follow a beat. I patted on his feet..12-123, and he matched the beat with a clap. This was new. And I asked him to spell cat, and as I started with c he added a and t. Same with bat. The best part is his group of teachers at the therapy center have noticed improvements across board.

And for me, the best part was when he planned out an attempt to hold our Alexandrian parakeet at my parents place using a napkin as our parrot was in an aggressive mood. Then he put his hands behind him and just tried to reach him with a kiss, accurately mimicking the parrots actions with the menacing open beak and curled tongue. His interactions with our dog are also more purposeful and affectionate.

But the downside is that visual stimming that he developed on bumetanide is not going away. And probably I had mentioned earlier, he is performing a curious act of running from switch board to switch board, stopping in front of each to gaze at the holes. This is a really mad act but I had read an autobiography written jointly by a morher-son, where the autistic son improved dramatically later in life and this child used to do the same wondering where these holes lead to and how and if they are connected. Probably wishful thinking on my part but what else can I do.

So Peter, in my son, even intermittent treatments leave some lasting impacts. And which include both negative and positive ones. Probably bumetsnide just disturbed his electrolyte balance and it might be a while before they are restored.

I am certain that even a good detox and antiinflammatory regime will support him with his natural progress. Wondering if I should trial clonazepam as I am wary of going for another round of diuretics till his sensitivities settle down. Or just start with antiinflammatories like kutki, taurine and low dose methylfolate.

The ability to mass edit genes directly via tools like CRISPR/Cas9 is still in its infancy and a lot more difficult than epigenetic retooling as there has been an enormous investment in drug research for epigenetic drugs/tools for the purposes of cancer research. IF there is a common epigenetic signature for autism (a very big IF) then reversing many of the symptoms of autism or at least improving them considerably may indeed be possible and may also be treated with drugs. This is just preliminary research, but it is the first I have seen to make any claims about a common epigenetic signature that most cases of autism share.

Here is some research directly pertinent to this topic in that new research (no paper unfortunately as it was a presentation or the Society of Neuroscience) which discusses how allergies can increase the risk of autism and specifically what seems to happen as a result of in-utero allergy exposure:

https://www.sciencedaily.com/releases/2016/11/161116155342.htm

One thing I found interesting about this is that I just read a paper discussing mechanisms of PTSD and what the researchers found in that paper is that a single bout of acute stress (not chronic stress) has a lasting impact of retracting dendritic spines in the prefrontal cortex via a cascade of events following a glutamate surge as a result of the acute stress. They found these stress insults to have significant effects on spine density and morphology for several weeks which was surprising because the conventional view was that only chronic stress like you see in depression can cause these kind of pathological features in dendritic spines.

Came across a few reports promoting and of obviously, demoting or dismissing and even warning against the use of resperine for autism, a therapy I think which got some publicity around 2010.

What caught my interest was an attempt at scientifically explaining why it might work for some autism. Women with a family history of depression, who get an epidural and pitocin during delivery if birthing male child might distort the enzymatic activity or levels of monoamine oxidase which supposedly plays critical role in conversions of certain neurotransmitters into their activated forms.

I did not really understand the entire hypothesis but I got an epidural and pitocin and probably was assisted with a vacuum as I remember the gynae who was in a real hurry to wind up telling me that she can see the babies head and it should be just a push or two. But after that I saw the nurse carrying something like a pump..there was an immediate birth cry and in the discharge summary it was written as NVD. And from my father's side we have what can be called as depression in some members but they mask it or rather, treat themselves by surrounding themselves with family and pets.

What would be your views be on MAO and could their be safer ways to increase its levels in the child as resperine is a psychoactive drug extracted from a plant hailing from, once again, India.

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By Agnieszka Wroczyńska, MD, PhD, Medical University of Gdansk, Poland In June 2014 my son with severe autism ...

About this Blog

This blog is mainly a review of the science behind autism, looking for pointers to effective treatments for classic autism.The first treatment, Bumetanide, I stumbled upon before starting this blog.The last treatment, tiny doses of Clonazepam, came from a recent paper, highlighted by a regular follower of this blog.You do need some basic scientific knowledge, but putting our minds together, we can make our own medical advances; so all comments and case histories are very welcome.

If your interest is regressive autism, very likely the cause is mitochondrial disease. Classic autism therapies may well be ineffective. Mitochondrial disease can be diagnosed and treated.

Quack-free zone - Science only

About Me

I am an independent researcher, trawling through the scientific literature and doing some experiments along the way. I am not a doctor. I do have a Master's degree from a top science-only university and another one from a top business school. More relevant is my motivation.

I am developing a novel drug therapy, the Autism Polypill, to treat classic early-onset autism, since this is the type that affects my son. His type of autism is characterized by autistic behaviours, pollen allergy, asthma, some SIB, high serotonin, high cholesterol, high euthyroid, high IGF-1, but without seizures, GI problems, food intolerance or severe MR. I think that ADHD and Asperger's are likely to be very mild forms of this phenotype of autism. Many other types of "autism" are entirely different. As this blog shows, at least classic autism is treatable using today's drugs.